Down-regulation of Androgen Receptor Expression and Inhibition of Lacrimal Gland Cell Proliferation by Retinoic Acid

Ubels, John L.; Wertz, John T.; Ingersoll, Kyle E.; Jackson, Roger S.; Aupperlee, Mark D.

doi:10.1006/exer.2002.2054

Cited by 24 publications

(17 citation statements)

References 42 publications

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“…Thus the effect of androgen was to antagonize that of atRA on hTGP expression (Figure 3B). Antagonistic effects of androgen and atRA have been previously described in both the prostate, where the activity of the AR was down-regulated, and expression of the PSA gene was negatively affected after atRA treatment (39,50,51) and in lacrimal gland cells (52). Interestingly, AR receptor knockdown showed that AR was positively regulating hTGP transcription in the absence of androgens (Figures 3D and 4A) and that this positive regulation was not via up-regulation of the RARs (Figure 4B).…”

Section: Discussionmentioning

confidence: 86%

Retinoic acid and androgen receptors combine to achieve tissue specific control of human prostatic transglutaminase expression: a novel regulatory network with broader significance

Rivera-Gonzalez

Droop

Rippon

et al. 2012

Nucleic Acids Research

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In the human prostate, expression of prostate-specific genes is known to be directly regulated by the androgen–induced stimulation of the androgen receptor (AR). However, less is known about the expression control of the prostate-restricted TGM4 (hTGP) gene. In the present study we demonstrate that the regulation of the hTGP gene depends mainly on retinoic acid (RA). We provide evidence that the retinoic acid receptor gamma (RAR-G) plays a major role in the regulation of the hTGP gene and that presence of the AR, but not its transcriptional transactivation activity, is critical for hTGP transcription. RA and androgen responsive elements (RARE and ARE) were mapped to the hTGP promoter by chromatin immunoprecipitation (ChIP), which also indicated that the active ARE and RARE sites were adjacent, suggesting that the antagonistic effect of androgen and RA is related to the relative position of binding sites. Publicly available AR and RAR ChIP-seq data was used to find gene potentially regulated by AR and RAR. Four of these genes (CDCA7L, CDK6, BTG1 and SAMD3) were tested for RAR and AR binding and two of them (CDCA7L and CDK6) proved to be antagonistically regulated by androgens and RA confirming that this regulation is not particular of hTGP.

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Section: Discussionmentioning

confidence: 86%

Retinoic acid and androgen receptors combine to achieve tissue specific control of human prostatic transglutaminase expression: a novel regulatory network with broader significance

Rivera-Gonzalez

Droop

Rippon

et al. 2012

Nucleic Acids Research

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“…These effects appear to be mediated through receptor-dependent and –independent actions (Nelson and others 2006; Tsukada and others 2000) and alterations in gene expression (Nelson and others 2008). In addition, RA may suppress androgen receptors (Ubels and others 2003; Ubels and others 2002) and inhibit retinol dehydrogenase-4 in sebaceous glands (Karlsson and others 2003), which would diminish the local, intracrine production of dihydrotestosterone (DHT). Of interest, specific deletion of scd-1 in the mouse skin causes a robust elevation of retinol, RA and RA-induced genes in the skin (Flowers and others 2011).…”

Section: Anti-aging Treatment- Potential Influence On Mgd and Dry Eyementioning

confidence: 99%

Aging and dry eye disease

Ding

Sullivan

2012

Experimental Gerontology

134

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Dry eye disease is a prevalent eye disorder that in particular affects the elderly population. One of the major causes of dry eye, meibomian gland dysfunction (MGD), shows increased prevalence with aging. MGD is caused by hyperkeratinization of the ductal epithelium of meibomian gland and reduced quantity and/or quality of meibum, the holocrine product that stabilizes and prevents the evaporation of the tear film. Of note, retinoids which are used in current anti-aging cosmetics may promote the development of MGD and dry eye disease. In this review, we will discuss the possible mechanisms of age-related MGD.

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“…However, it is noteworthy that some of the most significant testosterone actions are directed towards stimulation of mitotic cycles, DNA replication, DNA-dependent ATPase activity and chromosomal components. These molecular responses may underlie several biological effects of androgens on the lacrimal gland, including induction of epithelial cell proliferation (rabbit [14,21]) and a pronounced rise in tissue weight (mouse [22,23]). …”

Section: Discussionmentioning

confidence: 99%

“…In support of these hypotheses, lacrimal glands have been shown to contain a single class of saturable, high-affinity, steroid-specific and DNA-adherent androgen binding sites, that are located predominantly within epithelial cell nuclei [4][5][6][7][8][9]. Furthermore, androgens have been demonstrated to modulate the levels of several lacrimal gland mRNAs [1], and androgen action in lacrimal tissue or in isolated acinar epithelial cells may be suppressed by antagonists of, or mutations within, androgen receptors, as well as by inhibitors of transcription and translation [10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%